ICH Q7 clause 14: Rejection and re-use of materials

Rejected materials must be immediately segregated to prevent use. Quarantine procedures apply: distinctive labeling (typically red), physical separation, access control. Disposition options (per the remainder of Section 14): reprocessing (repeat established step), reworking (new step), recovery (solvent/material recovery), destruction, or use as different product with justification. QA approval of disposition is mandatory.

Reprocessing is the FIRST option for recovering out-of-specification material. It involves repeating a step that's already in the established process. Example: if a crystallization gives material with high impurity, repeating crystallization typically reduces impurity. Reprocessing maintains the validated process. If reprocessing is needed routinely, the process itself should be modified because routine reprocessing indicates process robustness issues.

This clause distinguishes normal process continuation (e.g., continuing a reaction after IPC shows incomplete) from reprocessing (re-starting a step after completion). Normal continuation is routine. Reprocessing requires impurity profile comparison to verify that reprocessing hasn't introduced new impurities or altered the profile. Any significant changes trigger investigation and potential batch rejection.

Unusual reprocessing (not part of established process) requires special handling. The QU must evaluate: scientific justification (why this step will work), impact on quality (impurity profile, yield, physical properties), impact on downstream steps, validation needs. Change control provides the governance framework. The before/after assessment provides direct evidence of the reprocessing outcome.

Reworking is distinct from reprocessing: reworking uses a step NOT in the established process. Example: if a batch has high impurities that crystallization can't remove, chromatographic purification (a new step) might be applied. Reworking requires: investigation into why the batch failed, scientific justification for the rework step, concurrent validation (protocol-based), extensive testing, and stability assessment if the rework could affect stability. The reworked batch must match quality of established-process batches.

Reworking with new process steps may introduce new impurities not seen in the normal process. These must be identified, quantified, and assessed for safety. ICH Q3A provides thresholds: below identification threshold = no action; above identification = characterization needed; above qualification = safety assessment needed. The reworked batch's impurity profile must meet the API specification. Historical data provides the comparison baseline.

Reworked batches receive enhanced scrutiny beyond routine release testing. Additional tests depend on the rework type: chromatographic rework might require additional impurity testing; physical rework (re-crystallization from a different solvent) might require polymorph testing; aqueous rework might require additional moisture and microbial testing. The enhanced testing demonstrates that the rework hasn't compromised quality.

Recovery is common in API manufacturing for economic and environmental reasons. Mother liquors often contain significant product that can be crystallized again. Solvents can be distilled and reused. Both are acceptable with proper controls: written procedures, specifications for recovered material, testing to verify quality, appropriate use of recovered material (same process preferred, different process acceptable with assessment). Recovery reduces waste and costs.

Recovered solvent quality may differ from fresh solvent. Impurities picked up during the prior use may persist even after distillation (e.g., high-boiling impurities). Specifications for recovered solvents should account for this — either maintaining original specs (strict) or defining modified specs suitable for the reuse application. Testing verifies compliance. Records link specific recovered batches to their testing and usage.

Blending fresh and recovered solvents is a common practice that reduces waste while maintaining quality. The blend must be tested to verify suitability. Records must maintain traceability: fresh solvent source, recovered solvent batch(es), blending ratio, resulting blend testing. For the batch record, the solvent source may need to be indicated, especially for validation batches or when traceability is critical.

Returned materials have experienced conditions outside the manufacturer's control — storage at the customer, transport back, potential contamination or damage. Quarantine prevents use until assessment is complete. The assessment considers: container integrity, storage conditions at customer (if known), reason for return (overstocked vs quality concern), shipping conditions during return. Materials with any doubt should be reprocessed, reworked, or destroyed — not simply reshelved.

Return records are essential traceability. Required content: consignee details (who returned it), product identification (name + batch), quantity returned, reason for return (customer's explanation), investigation findings, disposition decision (restock, rework, destroy), disposition date. These records support trending to identify recurring issues with specific products, customers, or batches.

The absolute rule: never mix returns with fresh stock until assessment is complete. Reintroduction to inventory after acceptable assessment is possible but requires: container integrity verification, re-testing (often a subset appropriate for the return circumstances), QA approval, documentation of the reintroduction decision. The reintroduced material should be tracked as 'returned' in inventory to enable later investigation if quality issues arise.